TABLE 3.

Antidepressant drug–drug–drug interaction signals with semi‐Bayes shrunk adjusted rate ratios for unintentional traumatic injury greater than or equal to two, by antidepressant and therapeutic category of co‐dispensed drug

Antidepressant	Therapeutic class of co‐dispensed drug of the base‐pair	Co‐dispensed drug of the base‐pair	Candidate interacting precipitant	RR, semi‐Bayes shrunk and adjusted a	95% CI
Amitriptyline	Cardiovascular	Losartan	Nitrofurantoin	2.36	1.18–4.72
	Endocrine and metabolic	Levothyroxine	Tizanidine	2.31	1.34–3.99
		Levothyroxine	Celecoxib	2.02	1.01–4.06
Bupropion	Cardiovascular	Losartan	Zolpidem	2.07	1.13–3.80
Citalopram	Cardiovascular	Simvastatin	Sulfamethoxazole	2.26	1.54–3.32
		Simvastatin	Trimethoprim	2.21	1.50–3.25
		Atorvastatin	Cefuroxime	2.44	1.29–4.62
		Isosorbide mononitrate	Sulfamethoxazole	2.20	1.25–3.88
		Rosuvastatin	Sulfamethoxazole	2.33	1.23–4.40
		Rosuvastatin	Trimethoprim	2.33	1.23–4.40
		Isosorbide mononitrate	Trimethoprim	2.11	1.20–3.69
		Atenolol	Sulfamethoxazole	2.01	1.13–3.56
		Atenolol	Trimethoprim	2.01	1.13–3.56
		Lisinopril	Losartan	2.06	1.11–3.80
		Enalapril	Sulfamethoxazole	2.19	1.04–4.63
		Enalapril	Trimethoprim	2.17	1.03–4.55
	Central nervous system	Olanzapine	Lorazepam	2.28	1.05–4.94
		Gabapentin	Buspirone	2.24	1.22–4.13
		Clonazepam	Tramadol	2.10	1.24–3.57
		Donepezil	Trimethoprim	2.09	1.35–3.24
		Donepezil	Sulfamethoxazole	2.08	1.34–3.24
		Memantine	Azithromycin	2.07	1.08–3.96
	Endocrine and metabolic	Norethindrone	Fluconazole	2.94	1.43–6.06
		Ethinyl estradiol	Fluconazole	2.67	1.31–5.44
		Levothyroxine	Sulfamethoxazole	2.38	1.73–3.29
		Levothyroxine	Trimethoprim	2.20	1.60–3.04
		Levothyroxine	Tizanidine	2.00	1.24–3.24
	Renal and genitourinary	Finasteride	Sulfamethoxazole	2.36	1.16–4.82
		Finasteride	Trimethoprim	2.36	1.16–4.82
		Tamsulosin	Amoxicillin	2.23	1.36–3.66
		Oxybutynin	Lisinopril	2.19	1.25–3.84
Duloxetine	Cardiovascular	Carvedilol	Nitrofurantoin	2.15	1.12–4.12
		Losartan	Tamsulosin	2.14	1.03–4.47
		Simvastatin	Donepezil	2.10	1.12–3.91
	Central nervous system	Tizanidine	Dicyclomine	2.63	1.31–5.27
		Zolpidem	Meloxicam	2.27	1.33–3.89
	Endocrine and metabolic	Allopurinol	Pregabalin	2.58	1.19–5.60
	Gastrointestinal	Pantoprazole	Mirabegron	2.16	1.03–4.52
	Hematological	Warfarin	Diazepam	2.25	1.04–4.89
Escitalopram	Cardiovascular	Simvastatin	Aripiprazole	6.60	3.23–13.46
		Olmesartan	Clonazepam	4.35	2.09–9.07
		Benazepril	Trimethoprim	2.89	1.35–6.16
		Rosuvastatin	Dexlansoprazole	2.80	1.19–6.59
		Atenolol	Sulfamethoxazole	2.76	1.49–5.13
		Atenolol	Trimethoprim	2.76	1.49–5.13
		Simvastatin	Pregabalin	2.49	1.16–5.35
		Pravastatin	Baclofen	2.48	1.13–5.43
		Benazepril	Sulfamethoxazole	2.44	1.14–5.25
		Terazosin	Alprazolam	2.38	1.06–5.34
		Simvastatin	Clonazepam	2.34	1.38–3.97
		Metoprolol	Naproxen	2.15	1.32–3.52
		Diltiazem	Doxycycline	2.14	1.14–4.02
		Atorvastatin	Carbidopa	2.13	1.17–3.88
		Atorvastatin	Levodopa	2.13	1.17–3.88
		Lisinopril	Divalproex	2.03	1.05–3.92
	Central nervous system	Memantine	Divalproex	2.36	1.28–4.36
		Carbidopa	Sulfamethoxazole	2.35	1.18–4.68
		Carbidopa	Trimethoprim	2.35	1.18–4.68
		Levodopa	Sulfamethoxazole	2.35	1.18–4.68
		Levodopa	Trimethoprim	2.35	1.18–4.68
		Morphine	Ondansetron	2.28	1.01–5.15
		Gabapentin	Loperamide	2.23	1.04–4.79
		Ropinirole	Naproxen	2.20	1.00–4.85
		Clonazepam	Aripiprazole	2.18	1.08–4.41
		Risperidone	Tramadol	2.08	1.02–4.25
		Memantine	Furosemide	2.04	1.22–3.42
	Endocrine and metabolic	Levothyroxine	Aripiprazole	2.94	1.63–5.29
		Levothyroxine	Sumatriptan	2.15	1.09–4.24
		Levothyroxine	Clonazepam	2.14	1.41–3.24
		Allopurinol	Sulfamethoxazole	2.13	1.07–4.23
		Allopurinol	Trimethoprim	2.13	1.07–4.23
		Alendronate	Trimethoprim	2.10	1.05–4.19
		Alendronate	Sulfamethoxazole	2.07	1.03–4.15
	Gastrointestinal	Ranitidine	Alprazolam	2.13	1.12–4.05
	Hematological	Clopidogrel	Loperamide	2.63	1.25–5.51
	Renal and genitourinary	Solifenacin	Sulfamethoxazole	2.99	1.55–5.79
		Solifenacin	Trimethoprim	2.84	1.46–5.51
		Oxybutynin	Codeine	2.62	1.26–5.46
		Hydrochlorothiazide	Sulfamethoxazole	2.46	1.61–3.77
		Hydrochlorothiazide	Trimethoprim	2.37	1.55–3.64
Fluoxetine	Cardiovascular	Pravastatin	Levofloxacin	2.41	1.19–4.90
		Diltiazem	Gabapentin	2.10	1.01–4.37
		Metoprolol	Sulfamethoxazole	2.08	1.22–3.57
	Central nervous system	Alprazolam	Fluconazole	2.48	1.23–4.99
	Endocrine and metabolic	Metformin	Clonazepam	2.74	1.40–5.36
	Gastrointestinal	Esomeprazole	Cyclobenzaprine	2.18	1.08–4.39
	Renal and genitourinary	Triamterene	Oxycodone	2.25	1.08–4.67
		Spironolactone	Amoxicillin	2.23	1.04–4.78
Mirtazapine	Cardiovascular	Diltiazem	Amoxicillin	2.92	1.55–5.50
		Diltiazem	Clavulanate	2.51	1.23–5.12
		Pravastatin	Sulfamethoxazole	2.22	1.08–4.55
		Metoprolol	Cefdinir	2.02	1.03–3.97
		Digoxin	Tramadol	2.00	1.08–3.70
	Endocrine and metabolic	Levothyroxine	Risperidone	2.09	1.11–3.94
Paroxetine	Cardiovascular	Benazepril	Amoxicillin	2.31	1.10–4.82
		Lovastatin	Tramadol	2.22	1.06–4.67
		Losartan	Baclofen	2.17	1.01–4.67
		Amlodipine	Meclizine	2.05	1.01–4.19
	Endocrine and metabolic	Ethinyl estradiol	Cyclobenzaprine	2.16	1.08–4.30
Sertraline	Cardiovascular	Atenolol	Sulfamethoxazole	2.63	1.54–4.51
		Atenolol	Trimethoprim	2.62	1.53–4.48
		Diltiazem	Sulfamethoxazole	2.55	1.40–4.65
		Diltiazem	Trimethoprim	2.44	1.34–4.42
		Lisinopril	Loperamide	2.41	1.33–4.38
		Terazosin	Levofloxacin	2.40	1.12–5.13
		Atorvastatin	Ropinirole	2.14	1.11–4.15
		Diltiazem	Ondansetron	2.01	1.10–3.69
	Central nervous system	Clonazepam	Loperamide	2.41	1.06–5.48
		Pregabalin	Doxycycline	2.10	1.08–4.06
		Meloxicam	Gabapentin	2.07	1.17–3.68
		Donepezil	Sulfamethoxazole	2.04	1.24–3.34
	Endocrine and metabolic	Levonorgestrel	Cyclobenzaprine	2.32	1.01–5.31
		Levothyroxine	Megestrol	2.11	1.15–3.88
		Levothyroxine	Metolazone	2.05	1.03–4.08
		Allopurinol	Sulfamethoxazole	2.02	1.08–3.77
	Hematological	Warfarin	Sulfamethoxazole	2.34	1.31–4.17
		Warfarin	Trimethoprim	2.25	1.27–4.00
		Warfarin	Gabapentin	2.06	1.24–3.43
		Clopidogrel	Quetiapine	2.01	1.15–3.52
	Renal and genitourinary	Solifenacin	Trimethoprim	2.84	1.36–5.96
		Solifenacin	Sulfamethoxazole	2.67	1.26–5.64
		Oxybutynin	Trimethoprim	2.31	1.31–4.08
		Oxybutynin	Sulfamethoxazole	2.29	1.29–4.07
Trazodone	Cardiovascular	Isosorbide mononitrate	Gabapentin	2.51	1.24–5.09
		Atorvastatin	Terbinafine	2.41	1.12–5.17
		Pravastatin	Alprazolam	2.33	1.25–4.34
		Atenolol	Sulfamethoxazole	2.03	1.05–3.95
	Central nervous system	Tramadol	Gabapentin	2.04	1.14–3.66
		Quetiapine	Clonazepam	2.03	1.07–3.86
		Meloxicam	Gabapentin	2.00	1.18–3.39
	Endocrine and metabolic	Glimepiride	Meclizine	2.15	1.01–4.59
	Renal and genitourinary	Spironolactone	Ciprofloxacin	2.30	1.26–4.22
		Furosemide	Promethazine	2.29	1.29–4.06
	Respiratory	Montelukast	Promethazine	2.13	1.00–4.54
Venlafaxine	Cardiovascular	Simvastatin	Sulfamethoxazole	2.11	1.12–3.97
		Simvastatin	Trimethoprim	2.06	1.10–3.86
	Hematological	Clopidogrel	Methylprednisolone	2.16	1.02–4.59

Abbreviations: CI, confidence interval; RR, rate ratio.

^a Rate ratio was calculated as outcome rates during candidate interacting precipitant‐exposed days divided by outcome rates during candidate interacting precipitant–unexposed days (i.e., $\frac{{\text{rate}}_{\text{base}-\text{pair}+\text{candidate interacting precipitant}}}{{\text{rate}}_{\text{base}-\text{pair}-\text{only}}}$), adjusting for the following time‐varying covariates: average daily dose of antidepressant, follow‐up month, and ever having a prior traumatic injury of interest.